“…This is the case, for example, for topaquinone, the enzymatic quinonoid cofactor of the ubiquitous copper amine oxidases. Nucleophilic attack by the amine substrate on the cofactor forms a carbinolamine intermediate that initiates the reaction (20). Removal of water results in an imine, via which proton abstraction of the R-carbon atom yields an intermediate of the Schiff base type.…”
Section: Reaction Of 25-dimethyl-p-benzoquinonediimine 4 With 6-[ 13 C]mentioning
2,5-Dimethyl- p-benzoquinonediimine was used as a model to study the reactivity of p-benzoquinonediimines, the first oxidation intermediates of allergenic p-amino aromatic compounds, toward lysine, as it has been suggested that this amino acid could play a key role in the induction mechanism of allergic contact dermatitis for a number of chemicals. The use of 6-[ (13)C]lysine and Nalpha-acetyl-6-[ (13)C]lysine, in association with (13)C NMR and HPLC in tandem with mass spectrometry techniques, allowed the identification of 4-amino-2,5-dimethylformanilide, 4-amino-2,5-dimethyl[ (13)C]formanilide, and the derivative containing the amino acid covalently bound at the para position. While enzymatic N-acetylation of p-phenylenediamine (PPD) has been described in the literature, in human skin for example, to our knowledge this was the first time that N-formylation of a PPD derivative induced by the reaction with an amino acid such as lysine was observed in solution, together with the formation of an adduct with the amino acid. To afford an explanation for the lysine-induced N-formylation,we undertook mechanistic studies, and they showed that 2,5-dimethyl- p-benzoquinonediimine was involved in an oxido reduction process that is capable of deaminating the alpha-NH 2 group, even when N-acetylated, and the epsilon-NH 2 groups of lysine in an oxidative way, forming the real reactive intermediates for N-formylation. This initially unexpected behavior should be considered when investigating the reactivity of such compounds with lysine-containing peptides or proteins in the context of hapten-protein binding studies.
“…This is the case, for example, for topaquinone, the enzymatic quinonoid cofactor of the ubiquitous copper amine oxidases. Nucleophilic attack by the amine substrate on the cofactor forms a carbinolamine intermediate that initiates the reaction (20). Removal of water results in an imine, via which proton abstraction of the R-carbon atom yields an intermediate of the Schiff base type.…”
Section: Reaction Of 25-dimethyl-p-benzoquinonediimine 4 With 6-[ 13 C]mentioning
2,5-Dimethyl- p-benzoquinonediimine was used as a model to study the reactivity of p-benzoquinonediimines, the first oxidation intermediates of allergenic p-amino aromatic compounds, toward lysine, as it has been suggested that this amino acid could play a key role in the induction mechanism of allergic contact dermatitis for a number of chemicals. The use of 6-[ (13)C]lysine and Nalpha-acetyl-6-[ (13)C]lysine, in association with (13)C NMR and HPLC in tandem with mass spectrometry techniques, allowed the identification of 4-amino-2,5-dimethylformanilide, 4-amino-2,5-dimethyl[ (13)C]formanilide, and the derivative containing the amino acid covalently bound at the para position. While enzymatic N-acetylation of p-phenylenediamine (PPD) has been described in the literature, in human skin for example, to our knowledge this was the first time that N-formylation of a PPD derivative induced by the reaction with an amino acid such as lysine was observed in solution, together with the formation of an adduct with the amino acid. To afford an explanation for the lysine-induced N-formylation,we undertook mechanistic studies, and they showed that 2,5-dimethyl- p-benzoquinonediimine was involved in an oxido reduction process that is capable of deaminating the alpha-NH 2 group, even when N-acetylated, and the epsilon-NH 2 groups of lysine in an oxidative way, forming the real reactive intermediates for N-formylation. This initially unexpected behavior should be considered when investigating the reactivity of such compounds with lysine-containing peptides or proteins in the context of hapten-protein binding studies.
“…Natural enzymatic transformations provide a great source of inspiration for developing new catalysts and reactions. The copper amine oxidases (CuAOs), which are involved in the metabolism of amines, have been the basis for developing the biomimetic amine oxidation process. In 1990, Klinman first identified the cofactor of CuAOs, isolated from bovine serum amine oxidase, as TPQ (2,4,5-trihydroxyphenylalanine quinone).…”
We
report herein our mechanistic studies of the ortho-quinone-catalyzed aerobic oxidation of primary, secondary, and tertiary
amines. Two different catalytic pathways were discovered for the reductive
half reactions: for primary amines, the reaction was found to proceed
via a transamination pathway, while the reactions with secondary amines
and tertiary amines proceeded via hydride transfer. We also found
that the amine substrates could significantly promote the regeneration
of the ortho-quinone catalyst in the oxidative half
reaction, in which a proton transfer occurs between the amine substrates
and catechol derivatives (the reduced form of the ortho-quinone catalyst).
“…Even though we were mainly interested in the iminoquinone form of TTQ (see Figure ), as this is the form of the cofactor just before the H + transfer, we also derived force-field parameters for TTQ in its native form. In part, this was done for completeness, but more importantly, it was done because many of the parameters used to describe native TTQ can also be used to describe other novel quinone cofactors whose experimental study has received a lot of attention in the past several years. , 3 Structure of TTQ in the iminoquinone form: (a) unprotonated, (b) protonated.…”
We have obtained AMBER94 force-field parameters for the TTQ cofactor of the enzyme methylamine dehydrogenase (MADH). This enzyme catalyzes the oxidation of methylamine to produce formaldehyde and ammonia. In the rate-determining step of the catalyzed reaction, a proton is transferred from the methyl group of the substrate to residue Asp76. We used the new parameters to perform molecular dynamics simulations of MADH in order to characterize the dynamics of the active site prior to the proton-transfer step. We found that only one of the oxygen atoms of Asp76 can act as an acceptor of the proton. The other oxygen interacts with Thr122 via a strong hydrogen bond. In contrast, because of the rotation the methyl group of the substrate, the three methyl hydrogen atoms are alternately in position to be transferred. The distance that the proton has to travel presents a broad distribution with a peak between 1.0 and 1.1 A and reaches values as short as 0.8 A. The fluctuation of the distance between the donor and the acceptor has the largest frequency component at 50 cm(-1), but the spectrum presents a rich structure between 10 and 400 cm(-1). The more important peaks appear below 250 cm(-1).
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